PhD Programme in Molecular Biomedicine, Department of Life Sciences, University of Trieste, Via E. Weiss 2, 34128 Trieste, Italy.
Laboratory of Regulatory and Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy.
Cells. 2021 Apr 25;10(5):1015. doi: 10.3390/cells10051015.
Ubiquitination is a post-translational modification that has pivotal roles in protein degradation and diversified cellular processes, and for more than two decades it has been a subject of interest in the biotech or biopharmaceutical industry. Tripartite motif (TRIM) family proteins are known to have proven E3 ubiquitin ligase activities and are involved in a multitude of cellular and physiological events and pathophysiological conditions ranging from cancers to rare genetic disorders. Although in recent years many kinds of E3 ubiquitin ligases have emerged as the preferred choices of big pharma and biotech startups in the context of protein degradation and disease biology, from a surface overview it appears that TRIM E3 ubiquitin ligases are not very well recognized yet in the realm of drug discovery. This article will review some of the blockbuster scientific discoveries and technological innovations from the world of ubiquitination and E3 ubiquitin ligases that have impacted the biopharma community, from biotech colossuses to startups, and will attempt to evaluate the future of TRIM family proteins in the province of E3 ubiquitin ligase-based drug discovery.
泛素化是一种翻译后修饰,在蛋白质降解和多样化的细胞过程中起着关键作用,二十多年来,它一直是生物技术或生物制药行业感兴趣的主题。三基序(TRIM)家族蛋白已被证实具有 E3 泛素连接酶活性,并参与多种细胞和生理事件以及生理病理状况,从癌症到罕见的遗传疾病。尽管近年来,许多种 E3 泛素连接酶已成为大型制药公司和生物技术初创公司在蛋白质降解和疾病生物学方面的首选,但从表面上看,TRIM E3 泛素连接酶在药物发现领域还没有得到很好的认识。本文将回顾泛素化和 E3 泛素连接酶领域的一些重磅科学发现和技术创新,这些发现和技术创新对生物制药界产生了影响,从生物技术巨头到初创企业,并将尝试评估 TRIM 家族蛋白在 E3 泛素连接酶为基础的药物发现领域的未来。